Tenofovir 1% gel is an investigational vaginal microbicide intended to reduce the risk of transmission of HIV. Pregnant women and mothers who have recently given birth often maintain sexual activity, and research has shown that they may be at greater risk of HIV infection during pregnancy. Microbicides may be able to prevent HIV infection during pregnancy, which would also prevent fetal exposure to HIV. This study will test the safety of using tenofovir 1% gel in healthy, pregnant women and healthy, breastfeeding women.

Safety and tolerability in lactating women are assessed by number of specific Grade 2 or greater adverse events in laboratory abnormalities or genital/pelvic signs/symptoms

Safety and tolerability in infants of lactating mothers [ Time Frame: Measured at Day 14 ] [ Designated as safety issue: Yes ]

Safety and tolerability in infants of lactating mothers is defined as no inpatient admission (confirmed on review of medical records) with diagnosis of adverse event (AE) judged to be related to study product

Tenofovir levels in maternal blood or breast milk [ Time Frame: Measured at Day 6 or delivery, depending on cohort ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Presence of tenofovir in blood among infants of participants in the pregnancy and lactation cohorts [ Time Frame: Measured at Day 6 or delivery, depending on cohort ] [ Designated as safety issue: No ]

Impact of tenofovir gel exposure on the presence of select organisms associated with neonatal sepsis among participants in the pregnancy cohort, (e.g., Group B β-hemolytic streptococcus, Escherichia coli) [ Time Frame: Measured at Day 6 ] [ Designated as safety issue: No ]

Adherence to daily use of tenofovir 1% gel for 7 days and its acceptability among pregnant and lactating women [ Time Frame: Measured at Day 6 ] [ Designated as safety issue: No ]

One applicator of placebo gel administered vaginally for 7 consecutive days

Experimental: Lactation cohort, tenofovir gel

Lactating mothers will receive tenofovir gel.

Drug: Tenofovir 1% gel

One applicator of tenofovir 1% gel administered vaginally for 7 consecutive days

Other Names:

Tenovofir disproxil fumate

TDF

Experimental: Pregnancy cohort, tenofovir gel

Pregnant women will receive tenofovir gel.

Drug: Tenofovir 1% gel

One applicator of tenofovir 1% gel administered vaginally for 7 consecutive days

Other Names:

Tenovofir disproxil fumate

TDF

Detailed Description:

Microbicides are substances, like gels or foams, being developed that can be applied before intercourse to prevent transmission of HIV. Research has shown that pregnant women are still at risk of sexual transmission of HIV, and some research has suggested that pregnant women may be at increased risk of HIV infection. Microbicides may also aid in preventing mother-to-child transmission of HIV, because they might be a feasible alternative to oral or intravenous medications in regions where these methods are difficult to implement. In tests on healthy women the vaginal microbicide tenofovir 1% gel has been safe and well tolerated. This study will test the safety of tenofovir 1% gel in healthy, pregnant women and healthy, lactating women.

Participation in this study will last approximately 3 to 10 weeks. Pregnant women will be followed until approximately 2 weeks after delivery of their children, and lactating women will be followed for 3 weeks. Pregnant women will be given either the tenofovir 1% gel or a placebo gel to be applied daily for 7 days. Groups of pregnant women will be further divided according to how late into pregnancy they enroll.

Pregnant women will have study visits at enrollment, 6 days after enrollment, and at delivery. They will also participate in phone assessments 1, 3, and 14 days after enrollment and at delivery.

Lactating women will be given tenofovir 1% gel and have study visits at enrollment and 6 days after enrollment. They will also participate in phone assessments 1, 3, and 14 days after enrollment.

All participants will complete blood tests, physical exams, and assessments of adverse events.

Eligibility

Ages Eligible for Study:

18 Years to 40 Years

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Criteria

Pregnancy cohort, inclusion criteria:

Willing and able to provide written informed consent to be screened for and take part in the study, including participation of the infant after delivery

Willing and able to provide adequate locator information

Willing and able to communicate in written and spoken English

HIV uninfected

Current pregnancy that is viable and a singleton

Gestational age consistent with the following guidelines:

For Pregnancy Cohort Group 1, between 37 0/7 and 39 1/7 weeks (inclusive) at the enrollment visit (Day 0)

For Pregnancy Cohort Group 2, between 34 0/7 and 36 6/7 weeks (inclusive) at the enrollment visit (Day 0)

Pap result consistent with Grade 0 or satisfactory evaluation of a non-Grade 0 Pap result, per clinical judgment of site investigator or record (IoR)/designee), in the 12 calendar months prior to enrollment

Willing to abstain from using nonprescribed intravaginal products and practices (including douching and sex toys) or other investigational agent or device during study participation

Pregnancy cohort, exclusion criteria:

History of adverse reaction to any component of tenofovir 1% gel

Enrollment in any other investigational drug or device trial within 30 days prior to the enrollment visit (Day 0)

Currently breastfeeding

Use of vaginal medications within 48 hours prior to screening or enrollment (Day 0) (participant may return to complete study procedures after 48 hours have passed since use of vaginal medication)

Documented to have any of the following during the current pregnancy:

Ultrasound evidence of significant fetal congenital anomaly (in the opinion of the IoR or designee)

Laboratory abnormalities noted at screening, as specified in study protocol

Diagnosis of sexually transmitted infection (STI), including chlamydia, gonorrhea, and/or trichomoniasis, in the past 8 weeks prior to enrollment (Day 0), as assessed by participant report or review of medical record

Symptomatic vaginitis, including bacterial vaginosis (BV) and vulvovaginal candidiasis (asymptomatic evidence of BV and/or yeast is not exclusionary) at the time of enrollment (Day 0)

Use of oral and/or vaginal preparations of antibiotic or antifungal medications at screening or within 7 days of enrollment (Day 0)

Any social or medical condition that, in the investigator's opinion, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Lactation cohort, inclusion criteria:

Willing and able to provide written informed consent to be screened for and take part in the study

Willing and able to provide adequate locator information

Willing and able to communicate in spoken and written English

HIV uninfected

At enrollment, currently primarily breastfeeding a single healthy infant between the ages of 4 and 26 weeks (inclusive)

Intending to breastfeed during the period of anticipated study participation

Using an effective method of contraception at enrollment (Day 0) into lactation cohort and intending to use an effective method for the duration of scheduled study participation

Pap result consistent with Grade 0 or satisfactory evaluation of non-Grade 0 Pap result, per clinical judgment of site IoR/designee, in the 12 calendar months prior to enrollment (Day 0)

Willing to abstain from using nonprescribed intravaginal products and practices (including douching and sex toys) or other investigational agent or device during study participation

Lactation cohort, mother exclusion criteria:

Participation in pregnancy cohort

Infant excluded from participation

History of adverse reaction to any component of tenofovir 1% gel

Participation in investigational drug or device trial within 30 days prior to the enrollment visit (Day 0)

Use of vaginal medication(s) within 48 hours prior to screening or enrollment (Day 0) (participant may return to complete study procedures after 48 hours have passed since use of vaginal medication)

More than two infant feedings in a single day with nutrition other than own breast milk (e.g., formula, solids) within 7 days prior to screening or enrollment (Day 0)

At the time of enrollment (Day 0), participant report or clinical evidence of insufficient milk supply or mastitis, according to the judgment of the IoR/designee

Use of oral and/or vaginal preparations of antibiotic or antifungal medications at screening or within 7 days of enrollment (Day 0)

Any social or medical condition that, in the investigator's opinion, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Lactation cohort, infant inclusion criteria:

Mother consents for participation of both self and infant in lactation cohort

In general good health, as determined by clinical judgment of IoR/designee

Between the ages of 4 and 26 weeks (inclusive) at both screening and enrollment

Lactation cohort, infant exclusion criteria:

Any social or medical condition that, in the investigator's opinion, would make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136759